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A new study found that patients taking GLP-1s to treat type 2 diabetes have a lower risk of developing Alzheimer’s disease, potentially opening the door to another lucrative category for Novo Nordisk. Diabetes patients on GLP-1 drugs, including Novo’s Ozempic and Eli Lilly’s Mounjaro, were 12% less likely to develop the disease compared with patients taking non-GLP-1 antihyperglycemics, according to a study published Monday in Nature Medicine by researchers at the St. Louis Health Care system. The data raise a crucial question for Novo’s GLP-1 franchise. The Danish company is expected to have topline data later this year from two Phase 3 trials testing semaglutide, the active molecule in Ozempic, in Alzheimer’s. These trials are the most advanced of a GLP-1 in the disease. Does the Nature study mean these trials are likely to succeed? Novo’s EVOKE and EVOKE Plus trials are identical, each enrolling 1,840 patients with early Alzheimer´s who will receive an oral formulation of semaglutide or placebo. The drug will be dosed up to 14 mg once daily. That’s the same dose as Rybelsus, the oral form of semaglutide approved for diabetes. The primary endpoint of the studies is a change in patient scores on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a common scale used to measure cognitive decline, after two years of treatment. What kind of efficacy will semaglutide need to show in the twin trials to add Alzheimer’s to its label? Eisai and Biogen’s Leqembi was approved on the basis of slowing Alzheimer’s progression by 27% using the CDR-SB over 18 months. Lilly’s Kisunla achieved a 29% benefit on the scale among the overall population in its pivotal trial and a 36% benefit in patients with early Alzheimer’s. Both drugs are anti-amyloid antibodies. But there are reasons not to walk away from Monday’s study overly confident. First, preventing Alzheimer’s, as the study suggests semaglutide does in some diabetes patients, is not the same as treating it. And then there is a curious finding from a different endpoint: the risk of suicide. The Nature trial did not just look at Alzheimer’s disease, but a range of health conditions, including hepatic, renal, cardiovascular and blood diseases as well as infections. It also looked at the risks of developing neurological disorders, as summarized in the graph. The trial found a 10% reduction in the risk of suicidal ideation, attempt or intentional self-harm. That’s in sharp contrast with a different academic analysis of WHO adverse event data last summer that linked semaglutide to a 45% increase in risk of suicidal thoughts compared with other drugs in the WHO database. In fairness, the Nature analysis assessed a wide range of incretins — Ozempic, Mounjaro, Novo’s Victoza, Lilly’s Trulicity, Lilly and AstraZeneca’s Byetta and GSK’s Tanzeum. Maybe the overall reduction in suicidality was driven by the other drugs rather than semaglutide. Further, it suggests that the trial’s finding of a 12% reduction in Alzheimer’s risk might not automatically translate into a hit for the EVOKE trials. The publicly available data are largely mixed when it comes to these drugs and their ability to prevent Alzheimer’s disease. There could be a portent in an earlier study of Victoza, another of Novo’s GLP-1s. A study conducted by researchers at Imperial College London and presented at the CTAD meeting in 2020 showed that patients with mild Alzheimer’s given Victoza for a year had better scores than placebo patients on one rating scale — but not on the CDR-SB. And Jefferies analysts had a blunt take last week, writing in a note that they do not believe that the EVOKE trials will show a significant benefit. Semaglutide “may have some modest effects but likely has no real impact or benefit on amyloid or tangles,” they wrote on Jan. 14. That possibility could be why Lilly is not trialing its GIP/GLP-1 agonist Mounjaro in Alzheimer’s disease. After a decades-long effort to bring to market an Alzheimer’s drug, it finally has Kisunla — and if you have one drug approved for Alzheimer’s, why take a gamble on a second?

A father-and-son biotech with ties to Iceland and Philadelphia has put together a €26.5 million Series A to develop oral treatments for Alzheimer’s disease and other neurodegenerative conditions. Founded in 2015, Arctic Therapeutics will attempt to push forward work by Icelandic genomics researcher Hákon Hákonarson. His son, Ívar Hákonarson, runs things as CEO. The duo raised funds from a variety of American and European investors, including the charitable foundation of billionaire Jeffrey Lurie, who owns the NFL’s Philadelphia Eagles franchise. Alzheimer’s has thwarted drug developers for decades, thanks to a string of trial failures for therapies based on the amyloid theory — the idea that the disease can be treated, or even reversed, by removing the buildup of amyloid plaque from the brain. Only recently did the FDA approve two such drugs: Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla both demonstrated modest effects at improving patients’ cognition and function. Most efforts to develop amyloid-targeting Alzheimer’s drugs, including Leqembi and Kisunla, involve administration through intravenous infusions in order to more easily cross the blood-brain barrier. Historically, oral Alzheimer’s treatments are much harder to deliver to the brain than IV therapies. The Hákonarsons say they’ve found a way to solve those issues. Arctic’s lead program, AT-001, is a prodrug of an inexpensive antioxidant called N-acetyl cysteine (NAC). Sometimes used as a supplement, it’s been around for about 60 years. It’s currently used to treat Tylenol toxicity and polycystic ovary syndrome, as well as relieve mucus buildup in the lungs, and more. The elder Hákonarson, who is the director of the genomics center at the University of Pennsylvania’s medical school, told Endpoints News that NAC does not normally cross the blood-brain barrier, but Arctic altered the chemistry to make it both fat-soluble and brain-penetrant. By doing so, Hákonarson said AT-001 can prevent the buildup of amyloid plaque from occurring and break up deposits already in the brain. “Our drug is basically blocking any new aggregation,” Hákonarson said of the amyloid plaques. “The critical thing is obviously to try to get it in early, but once you stop and you block any ongoing aggregation and precipitation, the macrophages in the brain, they just remove it.” Arctic plans to first test its hypothesis in smaller disease populations, and last year it received approval from the EMA to start a Phase 2b/3 trial in a rare, familial form of dementia called hereditary cystatin C amyloid angiopathy (HCCAA). If it works in this indication, the plan is to expand into other forms of dementia and Alzheimer’s, according to Ívar Hákonarson. The HCCAA study is expected to last about a year, and an approval in the EU could come as early as the second half of 2026, he added. Arctic’s plans for US trials and a potential launch are still being finalized, but the company is hoping that an EMA approval could help move things along in the US. The biotech also expects to partner with a larger pharma company to commercialize the drug in the US if it’s approved. “Our goal is to get this treatment to the US as soon as possible,” Ívar Hákonarson said. “That is, of course, the largest market, which we will be targeting.” Arctic has another pipeline program called AT-004 that it will develop with the funding. The treatment is a topical solution being developed for a variety of skin conditions, including psoriasis and atopic dermatitis. The company expects to launch a Phase 2a study in acne vulgaris in Europe, and it completed its pre-IND meeting with the FDA for the program last year. In addition to the Lurie Family Foundation, other investors in the Series A included EIC Fund, Kaldbakur, Sanos Group, Cerebrum DAO, early investors and co-founders of Kerecis and ChemoMetec, and several institutional and family investors from Iceland. Editor’s note: This story was updated to correct the nature of two of the Series A investors. Early investors and co-founders of Kerecis and ChemoMetec — and not the companies — invested in Arctic.